The overall objective of this project is to understand the role of serum hormone binding proteins in normal physiology and in the pathophysiology of various human disease states. Novel methods with improved precision and sensitivity for the measurement of the principal human sex hormone transport proteins, testosterone-estradiol binding globulin (TeBG) and albumin, have been developed. Structure-function studies have revealed unexpectedly high affinity TeBG binding of a group of estrogen metabolites which have no intrinsic sex hormone activity, the 2-methoxyestrogens. Future directions of the project include (1) the development and characterization of an animal model in which the physiologic role of the steroid binding globulins can be investigated and (2) a detailed assessment of the nature of sex steroid transport throughout human development with particularly emphasis on puberty and its disorders.